Tumor suppressor gene, cell surface adhesion molecule, and multidrug resistance in Mullerian serous carcinomas: Clinical divergence without immunophenotypic differences

Objectives. We hypothesize that differences in the expression of selected t umor suppressor genes, cell surface adhesion molecules, and multidrug resis tance glycoproteins could account for some of the reported differences betw een uterine serous carcinoma (USC) and extrauterine serous carcinomas (ESC) , including ovarian and primary peritoneal carcinoma (OSC and PSC, respecti vely). Methods. We studied the expression of the following antigens in 20 USCs, 20 OSCs, and 10 PSCs: p53 and mdm-2 (tumor suppressor genes), CD44 and CD44v6 (cell surface adhesion molecules), and the p-glycoprotein (a multidrug res istance protein recognized by two antibodies, C494 and JSB1). We further st udied chemotherapeutic drug resistance by examining reports prepared using the Oncotech Extreme Drug Resistance Assay from 24 of the 50 study patients . Clinical data were obtained from medical record review. Results. USC, OSC, and PSC patients were similar with respect to mean age a t diagnosis, mean gravidity, mean parity, personal history of breast cancer , percentage treated with chemotherapy, and survival at 3 and 5 years postd iagnosis. Significant clinical differences included a high prevalence of nu lliparity in OSC (P = 0.05), a low prevalence of Caucasian race in USC (P = 0.008, a paucity of stage I patients in OSC and PSC (P = 0.03), a high pre valence of familial breast cancer in OSC (P = 0.06), and superior 2-year su rvival in OSC (P = 0.02). Seventy-five percent of USCs, 52% of OSCs, and 60 % of PSCs expressed p53. Five percent of USCs, 19% of OSCs, and 0% of PSCs expressed mdm-2. Forty percent of USCs, 33% of OSCs, and 10% of PSCs expres sed CD44. None of the USCs, OSCs, or PSCs expressed CD44v6. Sixty-one perce nt of USCs and OSCs and 82% of PSCs expressed C494 while 17% of USCs, 19% o f OSCs, and 20% of PSCs expressed JSB1. None of these apparent differences was statistically significant. USC, OSC, and PSCs patients did not demonstr ate significant differences with respect to extreme drug resistance. Howeve r, the following trends were noted (P = 0.06): more prevalent low drug resi stance for cyclophosphamide in OSC compared with USC and more prevalent ext reme drug resistance for etoposide in OSC compared with USC. Conclusions. Therefore, despite significant clincial differences, the USCs and ESCs in our series do not differ significantly with respect to the expr ession of the tumor suppressor genes, cell surface adhesion molecules, and drug resistance proteins studied. It is premature, however, to recommend th at USCs and ESCs should be treated identically. (C) 2000 Academic Press.